title: The impact of tumor necrosis factor α inhibitors on radiographic progression in ankylosing spondylitis.
abstract: OBJECTIVE
  To study the effect of tumor necrosis factor α (TNFα) inhibitors on progressive spinal damage in patients with ankylosing spondylitis (AS).
  
  
  METHODS
  All AS patients meeting the modified New York criteria who had been monitored prospectively and had at least 2 sets of spinal radiographs a minimum of 1.5 years apart were included in the study (n=334). The patients received standard therapy, which included nonsteroidal antiinflammatory drugs and TNFα inhibitors. Radiographic severity was assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Patients with a rate of AS progression that was ≥1 mSASSS unit/year were considered progressors. Univariable and multivariable regression analyses were done. Propensity score matching and sensitivity analysis were performed. A zero-inflated negative binomial (ZINB) model was used to analyze the effect of TNFα inhibitors on the change in the mSASSS with varying followup periods. Potential confounders, such as disease activity (as assessed by the Bath Ankylosing Spondylitis Disease Activity Index), the erythrocyte sedimentation rate, C-reactive protein level, HLA-B27 positivity, sex, age at onset, smoking burden (number of pack-years), and baseline damage, were included in the model.
  
  
  RESULTS
  TNFα inhibitor treatment was associated with a 50% reduction in the odds of progression, with an odds ratio (OR) of 0.52 (95% confidence interval [95% CI] 0.30-0.88, P=0.02). Patients with a delay of >10 years in starting therapy were more likely to experience progression as compared to those who started earlier (OR 2.4 [95% CI 1.09-5.3], P=0.03). In the ZINB model, the use of TNFα inhibitors significantly reduced disease progression when the gap between radiographs was >3.9 years. The protective effect of TNFα inhibitors was stronger after propensity score matching.
  
  
  CONCLUSIONS
  Treatment with TNFα inhibitors appears to reduce radiographic progression in AS patients, especially with early initiation and with longer duration of followup.
authors.affiliation: University Health Network and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nigil
authors.initials: N
authors.lastname: Haroon
authors.forename: Robert D
authors.initials: RD
authors.lastname: Inman
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Learch
authors.forename: Michael H
authors.initials: MH
authors.lastname: Weisman
authors.forename: MinJae
authors.initials: M
authors.lastname: Lee
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Rahbar
authors.forename: Michael M
authors.initials: MM
authors.lastname: Ward
authors.forename: John D
authors.initials: JD
authors.lastname: Reveille
authors.forename: Lianne S
authors.initials: LS
authors.lastname: Gensler
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015796:HLA-B27 Antigen / Q000097:blood; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011859:Radiography; D012720:Severity of Illness Index; D013131:Spine / Q000000981:diagnostic imaging; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D015796:HLA-B27 Antigen; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein